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Chemotherapy has been reported to upregulate sphingomylinases and increase cellular ceramide, often linked to the induction to cell death. In this work, we show that sublethal doses of doxorubicin and vorinostat still increased cellular ceramide, which was located predominantly at the plasma membrane. To interrogate possible functions of this specific pool of ceramide, we used recombinant enzymes to mimic physiological levels of ceramide at the plasma membrane upon chemotherapy treatment. Using mass spectrometry and network analysis, followed by experimental confirmation, the results revealed that this pool of ceramide acutely regulates cell adhesion and cell migration pathways with weak connections to commonly established ceramide functions (eg, cell death). Neutral sphingomyelinase 2 (nSMase2) was identified as responsible for the generation of plasma membrane ceramide upon chemotherapy treatment, and both ceramide at the plasma membrane and nSMase2 were necessary and sufficient to mediate these “side” effects of chemotherapy on cell adhesion and migration. This is the first time a specific pool of ceramide is interrogated for acute signaling functions, and the results define plasma membrane ceramide as an acute signaling effector necessary and sufficient for regulation of cell adhesion and cell migration under chemotherapeutical stress. Fil: Canals, Daniel. Stony Brook University; State University of New York; Fil: Salamone, Silvia. Stony Brook University; State University of New York; Fil: Santacreu, Bruno Jaime. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Nemeth, Erika. Stony Brook University; State University of New York; Fil: Aguilar, Daniel. Biomedical Research Networking Center in Hepatic and Digestive Diseases; España Fil: Hernandez Corbacho, María José. Stony Brook University; State University of New York; Fil: Adada, Mohamad. Stony Brook University; State University of New York; Fil: Staquicini, Daniela I.. Rutgers Cancer Institute of New Jersey; Estados Unidos Fil: Arap, Wadih. Rutgers Cancer Institute of New Jersey; Estados Unidos Fil: Pasqualini, Renata. Rutgers Cancer Institute of New Jersey; Estados Unidos Fil: Haley, John. Stony Brook University; State University of New York; Fil: Obeid, Lina M.. Stony Brook University; State University of New York; Fil: Hannun, Yusuf A.. Stony Brook University; State University of New York

Zusammenfassung Hintergrund Qualitätsindikatoren sind besonders im Notarzteinsatz, der häufig lebensrettenden Charakter hat, von großer Wichtigkeit. Ziel der Studie Das Ziel war, die Übereinstimmung zwischen notärztlicher Verdachtsdiagnose und Krankenhausentlassungsdiagnose und die diagnosebezogene Behandlungsdauer zu ermitteln, um zu prüfen, ob diese als Qualitätsindikatoren herangezogen werden können. Material und Methoden 708 Notarzteinsatzprotokolle des Notarztstandorts Bad Belzig im Zeitraum vom 01.07.2013 bis 30.06.2014 und 01.01.2015 bis 31.12.2015 wurden inkludiert. Die Ermittlung der dÜ (diagnostischen Übereinstimmung) erfolgte durch den Konsens dreier erfahrener Notfallmediziner. Die Behandlungsdauer wurde als Zeitintervall zwischen dem Zeitpunkt des Eintreffens des Notarztes und seiner Abfahrt vom Einsatzort berechnet. Die Behandlungsdauer wurde mittels des Mann-Whitney-U-Tests auf signifikante Unterschiede mit weiteren Variablen getestet. Aus der dÜ und der Behandlungszeit konnte die diagnostische Effizienz im Notarzteinsatz (dEffNA) ermittelt werden. Ergebnisse Die dÜ lag in 69,4% der Fälle vor. Die durchschnittliche Behandlungsdauer alle Einsätze dauerte 21 min. Die dEffNA ergab einen Durchschnittswert für alle Diagnosen von 3,3/min. Der beste Wert für die dEffNA (dEffNA-kurz) unter den 5 untersuchten einsatzbezogenen Entlassungsdiagnosen betrug 13/min für Apoplex und der schlechteste (dEffNA-lang) 1,15/min für hypertensive Entgleisung/Krise. Die Korrektheit der Notarztdiagnose schien unabhängig von der Behandlungsdauer zu sein. Diskussion Die dEffNA, berechnet aus dÜ und Behandlungszeit, kann als Qualitätsindikator in der präklinischen Notfallmedizin herangezogen werden. Mit dessen Hilfe können problematische Behandlungsfälle identifiziert werden.

The focus of this work is to test the security offered by Text-based CAPTCHAs. We present different types of CAPTCHAs and a preprocessing and segmentation process to clean noise in CAPTCHA images and crop digits or characters in single images. We present a convolutional neural network architecture trained under several hyperparameters, comparing multiple models with different batch sizes, epochs, and optimizers. We confirmed that using Text-based CAPTCHAs is no longer a secure mechanism for protection because, with simple computer vision techniques and current machine learning algorithms, they can be broken. We achieved a 90.49% accuracy with our model trained with a mix of four datasets and up to 97.10% with one dataset, which is enough to consider these schemes insecure in practice.

Introduction: Hypervirulent strains of Klebsiella pneumoniae have gained clinical and epidemiological interest because of their capacity to cause severe and life-threatening infections. Methodology: We report a case involving infection with a hypervirulent K. pneumoniae K2 strain that caused liver abscess in a young woman with type 1 diabetes in Mexico. Results: The infection was found to be associated with biliary tract communication. The virulence factors and capsular serotypes were identified by polymerase chain reaction analysis. After guided drainage and directed antibiotic treatment, the infection resolved and the patient recovered. Colonization of the gastrointestinal tract by hypervirulent K. pneumoniae strains, together with the presence of comorbidity, such as diabetes are important factors that contribute to the development of liver abscess. Conclusions: The identification of virulent clones is important to understand the pathogenicity and improve control of infections in the patients.

The purpose of this study was to investigate the acute effect of pre-activation with Variable Intra-Repetition Resistance and isometry on the overhead throwing velocity in handball players. Fourteen female handball players took part in the study (age: 21.2 ± 2.7 years, experience: 10.9 ± 3.5 years). For Post-Activation Potentiation, two pre-activation methods were used: (I) Variable Intra-Repetition Resistance: 1 x 5 maximum repetitions at an initial velocity of 0.6 m·s-1 and a final velocity of 0.9 m·s-1; (II) Isometry: 1 x 5 s of maximum voluntary isometric contraction. Both methods were "standing unilateral bench presses" with the dominant arm, using a functional electromechanical dynamometer. The variable analysed was the mean of the three overhead throws. Ball velocity was measured with a radar (Stalker ATS). The statistical analysis was performed using ANOVA with repeated measures. No significant differences were found for either method (variable resistance intra-repetition: p = 0.194, isometry: p = 0.596). Regarding the individual responses, the analysis showed that 86% of the sample increased throwing velocity with the variable resistance intra-repetition method, while 93% of the sample increased throwing velocity with the isometric method. Both the variable intra-repetition resistance and isometric methods show improvements in ball velocity in female handball players. However, the authors recommend checking individual responses, since the results obtained were influenced by the short rest interval between the pre-activation and the experimental sets.

Der Einfluss des Faktors „Patient“ auf die arztliche Diagnosestellung konnte bereits nachgewiesen werden. Zur praklinischen Diagnosestellung gibt es jedoch diesbezuglich keine Studien. Aus praklinischen Routinedaten konnen objektive Faktoren des Patientenzustands ausgewertet und deren Einfluss auf die Notarztdiagnose untersucht werden. Ziel dieser retrospektiven Pilotstudie war diagnostische Ubereinstimmung (dU) zwischen Notarzt- und Krankenhausentlassungsdiagnose zu ermitteln und den Einfluss der patientenspezifischen Faktoren „GCS“ (Glasgow Coma Scale), „Alter“, „NACA-Score“ (National Advisory Committee for Aeronautics), „Geschlecht“ und „Dauermedikation“ auf die dU zu untersuchen. Die Ermittlung der dU erfolgte durch den Konsens dreier erfahrener Notfallmediziner unter Verwendung der ICD-10-Kodierung. Die dU wurde bezuglich der 5 patientenspezifischen Faktoren zunachst univariat und anschliesend mittels multipler logistischer Regression auf signifikante Ergebnisse getestet. Weiterhin wurden die Korrelationskoeffizienten der kategorialen und nichtnormalverteilten Variablen und ein Goodness-of-Fit-Test (mittels Hosmer-Lemeshow-Test) berechnet. Eine dU bestand in 24 % (n = 138) nicht, sie bestand mindestens teilweise in 76 % (n = 442). Die untersuchten patientenspezifischen Faktoren zeigten keinen Einfluss auf die notarztliche Diagnosestellung. Der GCS-Summenwert des Patienten, sein Alter, der NACA-Score des Patienten, sein Geschlecht und seine Medikation scheinen keinen Einfluss auf die Qualitat der Notarztdiagnose zu haben. Andere Studien erbrachten einen Anteil von etwa 90 % korrekter Notarztdiagnosen, der als Benchmark dienen kann. Weitere Untersuchungen zu den Ursachen und Verbesserungspotenzial bei diagnostischer Ungenauigkeit sind erforderlich.

El grano y olote de maíz (Zea mays L.) de color morado son fuente de pigmentos, que pueden sustituir a los colorantes artificiales. El objetivo fue determinar el efecto del ambiente (temperatura) de producción de semilla en el contenido de antocianinas en grano (CATg) y olote (CATo) y su correlación en una población de maíz morado de Perú. Los ambientes de producción de semilla fueron Tepatitlán y La Huerta, Jalisco, México. Las semillas de los dos ambientes se sembraron en el ciclo PV 2015 en Tepatitlán, Jalisco. Se polinizaron de 100 a 130 plantas. A la cosecha, las mazorcas sanas y con el color de grano morado intenso, fueron analizadas por CATg y CATo mediante espectrofotometría. Se hizo un análisis de varianza y correlación de Person. El ambiente de producción de semilla afectó de manera significativa (p≤ 0.05) los contenidos de antocianinas en grano y olote. La semilla obtenida en Tepatitlán (temperatura. media 19.1 °C) presentó un CATg de 496.3 mg equivalentes de cianidina 3-glucósido en 100 g de muestra seca, que fue 57.6% superior al de la semilla procedente de La Huerta (temp. media 25.4 °C). El olote presentó entre 48 y 70% más antocianinas que el grano y perfil cromatográfico similar entre grano y olote. La correlación entre las variables de color de grano y el CATg no fue significativa (p≥ 0.05). Pero, la correlación negativa del valor de croma con CATo fue altamente significativa (r= -0.5484**) por lo que podría ser estimador del CAT en esta estructura.

We have analyzed the effect of the soluble guanylate cyclase (sGC) stimulator BAY 41-2272 in a therapeutic intervention in guinea pigs chronically exposed to cigarette smoke (CS). The effects of sGC stimulation on respiratory function, pulmonary hemodynamics, airspace size, vessel remodeling, and inflammatory cell recruitment to the lungs were evaluated in animals that had been exposed to CS for 3 mo. CS exposure was continued for an additional 3 mo in half of the animals and withdrawn in the other half. Animals that stopped CS exposure had slightly lower pulmonary artery pressure (PAP) and right ventricle (RV) hypertrophy than those who continued CS exposure, but they did not recover from the emphysema and the inflammatory cell infiltrate. Conversely, oral BAY 41-2272 administration stopped progression or even reversed the CS-induced emphysema in both current and former smokers, respectively. Furthermore, BAY 41-2272 produced a reduction in the RV hypertrophy, which correlated with a decrease in the PAP values. By contrast, the degree of vessel remodeling induced by CS remained unchanged in the treated animals. Functional network analysis suggested perforin/granzyme pathway downregulation as an action mechanism capable of stopping the progression of emphysema after sGC stimulation. The pathway analysis also showed normalization of the expression of cGMP-dependent serine/kinases. In conclusion, in guinea pigs chronically exposed to CS, sGC stimulation exerts beneficial effects on the lung parenchyma and the pulmonary vasculature, suggesting that sGC stimulators might be a potential alternative for chronic obstructive pulmonary disease treatment that deserves further evaluation.

[Resumen] El poder de una marca sobre los públicos, ha sido últimamente tema de estudio, dada la incidencia que esta ejerce sobre el comportamiento de compra y consumo de productos y servicios. De allí nace la aplicación del branding emocional herramienta adecuada para posicionar a la compañía a través de las emociones y lograr la fidelización de sus clientes. El propósito del presente trabajo es exponer si esta herramienta de gestión de marca influye en la fidelización de los clientes de Starbucks en la ciudad de Guadalajara. Se optó por el método cuantitativo, empleando la técnica de la encuesta y utilizando como instrumento un cuestionario en una muestra representativa conformada por 329 clientes. Los resultados nos permitieron explicar la influencia del branding emocional positivamente en la fidelización de los clientes. [Abstract] The power of branding is a growing area of study owing to its ability to influence spending and consumption decisions about products and services. Emotional branding is a way of positioning a company in the marketplace and securing brand loyalty by connecting with customer emotions. The aim of this study is to examine if Starbucks customer loyalty in the city of Guadalajara is influenced by branding. The analysis used a quantitative survey method involving a representative sample of 329 customers. The results showed that emotional branding has had a positive impact on customer loyalty among the survey population.

La investigación se centra en el lenguaje de programación utilizado en Code.org para el desarrollo del razonamiento lógico matemático en los niños de nivel medio de educación básica en el Ecuador, el cual se considera como el más idóneo para que los niños trabajen en la programación informática, ya que cuenta con una interfaz gráfica amigable y se programa sobre objetos, todo lo cual ayuda además a mejorar su desempeño en otras áreas. La vinculación de los conceptos Code.org, del lenguaje de programación y de la lógica matemática constituye la guía primordial de la investigación que, en definitiva, tiene como finalidad comprobar, en el contexto ecuatoriano, si la programación ejerce o no alguna influencia sobre la capacidad lógica matemática del niño, y, de ejercerla, de qué forma lo hace, cuál es su metodología y cuáles son los fundamentos pedagógicos en el proceso de enseñanza-aprendizaje. Los resultados finales reflejaron que la enseñanza del lenguaje de programación en Code.org estimula la capacidad lógico-matemática de los estudiantes, tanto de manera general como en cada uno de los indicadores estudiados.

Este artículo explora los recursos narrativos y visuales planteados en el cómic colombiano, desde 1992 hasta nuestros días, para describir representaciones distópicas de la ciudad de Bogotá. La distopía se entiende, en términos generales, como una visión negativa, para la humanidad, de un futuro posible o de un presente alterno, y se clasifica acá en distopías de fallo tecnológico, distopías de coerción simbólica/coerción física, distopías de apocalipsis zombie/infectado y distopías de apocalipsis sobrenatural/no humano. Para la investigación se recopilaron las publicaciones impresas disponibles desde 1992 (130 productos), de los cuales se seleccionaron aquellos que sucedieran o hicieran referencia a la ciudad de Bogotá. De los 45 cómics que cumplían dicho criterio, se identificaron y analizaron las 28 piezas que presentaron un escenario distópico. Entre los hallazgos fundamentales se encontró que la violencia y el conflicto, tanto simbólicos como físicos, son constantes en los diferentes escenarios distópicos identificados en la muestra, lo que refleja y proyecta la violencia histórica que vive un país como Colombia., This paper explores the narrative and visual resources used in Colombian comics, from 1992 to the present day, in order to describe dystopian representations of Bogotá city. Dystopia is generally understood as a negative view for humanity either of a possible future or an alternative present. These fictions are classified here as dystopias about a technological failure, dystopias about a symbolic/physical coercion, apocalyptic dystopias about zombies/infected individuals and apocalyptic dystopias about supernatural/non-human events. For this research study, printed publications available since 1992 (130 items) were collected. Out of these fictions, those that were set in or made reference to the city of Bogotá were selected. Of the 45 comics that met this criterion, 28 were identified and analyzed that contained a dystopian setting. One of the major findings was that violence and conflict, both symbolic and physical, are constant in the different dystopic settings identified in the study sample, which reflects and projects the historical violence experienced in Colombia.

La planta de Stevia rebaudiana Bertoni carece de trabajos con el enfoque científico sobre su posible propagación in vitro en el estado de Puebla, por ello, en junio de 2016 se evaluaron diferentes concentraciones de 6-Bencilaminopurina (0.0, 0.3, 0.5, 0.7 y 1.0 mg∙L-1) y tres condiciones de medio de cultivo para su micropropagación. Se realizó un análisis preliminar sobre la presencia de esteviósidos en el medio de cultivo después de obtener y multiplicar brotes de Stevia rebaudiana a partir de segmentos nodales sumergidos en el mismo por ocho semanas. Para el análisis de los datos sobre número y longitud de brotes in vitro se realizó un análisis de varianza completamente al azar y se empleó la prueba de Tukey (p=0.05) para determinar diferencias entre las medias de cada tratamiento mediante Minitab 16, donde la concentración de 0.5 mg∙L-1 de 6-Bencilaminopurina fue el tratamiento que originó mayor número de brotes in vitro (3.6 ± 1.4) y en cuanto al tipo de soporte, el medio de cultivo sin soporte (líquido) fue el mejor originando hasta 21.45 nuevos brotes. El análisis preliminar de esteviósidos se realizó mediante cromatografía en capa delgada observando la posible presencia de dichos metabolitos en el medio de cultivo.

En la presente investigación se planteó como objetivo general analizar jurídicamente la negligencia médica en la atención de accidentes de tránsito, Ibarra, Ecuador. Desde el paradigma cuantitativo, se maneja para este tipo de estudio, documentos, textos legales, investigaciones científicas mediante la recolección, selección y análisis de los mismo. El diseño bibliográfico-documental se apoyó en los procesos lógicos y mentales. Los investigadores organizaron un proceso investigativo en donde la población de estudio, se basó primordialmente en documentos escritos, normas, leyes, para indagar los escritos con el objeto de estudiarlos y construir conclusiones que favorecen en la generación de nuevos conocimientos. Se concluye que, la negligencia médica es aquella acción u omisión de la persona que conociendo su deber objetivo de cuidado actúa de forma irresponsable en el curso de atención de emergencias en este caso. De modo que, la cosmovisión nacional respecto a la atención pre hospitalaria en accidentes de tránsito.

Arturo Ortiz-Álvarez,1 Mónica A Delgado-Ramírez,1 Montserrat Cuevas-Zúñiga,1 Teresa Hernández-Carrera,1 David Moncada Barrón,2 Daniel Aguilar Zapata,1 Rafael R Valdez Vázquez,1 Juan Pablo Ramírez-Hinojosa,1 Ana Patricia Rodríguez-Zulueta1 1Department of Infectious Disease, Hospital General Dr. Manuel GEA González, Mexico City, Mexico; 2Microbiology Laboratory, Hospital General Dr. Manuel GEA González, Mexico City, Mexico Introduction: Outpatient parenteral antimicrobial therapy is a safe, effective, and convenient way of administering antimicrobials for a wide variety of infections. So far there are no reports on the efficacy of outpatient antimicrobial therapy in Mexico. Our objective was to determine the outcomes, safety, and cost of outpatient ertapenem therapy (OET) in our hospital. Patients and methods: A case series of 99 patients that received intravenous OET was conducted. The primary outcomes were clinical cure, relapse, and recurrence of infection. Results: Of the 99 patients who received OET the most common diagnosis was urinary tract infection in 56%. Extended-spectrum-β-lactamase-producing Enterobacteriaceae caused 67% of infections in our population. Ninety-seven percent of the patients were cured at the completion of OET. One patient presented relapse 12 days after the end of OET; two patients presented recurrence, one with skin and soft tissue infection and one with pyelonephritis at days 35 and 34, respectively, after the end of OET. Three patients were readmitted after OET, one with an episode of phlebitis, one with recurrence, and one with relapse. A case of non-Clostridium difficile-associated diarrhea was observed. The intravascular line complications observed during OET were phlebitis in two patients. Conclusion: In our hospital, the OET was found to be effective, safe, and cost-saving when compared to inpatient care. Keywords: OPAT, ESBL, ertapenem

Future spacecraft missions require novel guidance and control policies that reduce fuel consumption, yield sparse thrust signals, and maintain mission safety even in the presence of faults. This paper presents an approach for rendezvous with a target in a near-rectilinear halo orbit that exploits the natural dynamics to reduce propellant consumption, and ensures passive safety in the presence of thruster failure. A chaser spacecraft that aims to rendezvous with a target is steered into coasting sets while simultaneously maintaining passive safety by avoiding the states that naturally collide with the target. Upon entering the coasting sets, the chaser's thrusters are disengaged, as the natural dynamics lead it into a goal set. Abort-safety is then demonstrated during final approach from the goal set to the target. The target is modeled in a full-ephemeris, high-fidelity, and quasi-periodic near-rectilinear halo orbit. Simulations demonstrate a reduction in maneuver fuel consumption, measured by delta-v, of up to 72.5% and a significant reduction of thruster on-time compared to prior work.

We have recently reported that a specific pool of ceramide, located in the plasma membrane, mediated the effects of sublethal doses of the chemotherapeutic compound doxorubicin on enhancing cancer cell migration. We identified neutral sphingomyelinase 2 (nSMase2) as the enzyme responsible to generate this bioactive pool of ceramide. In this work, we explored the role of members of the protein phosphatases 1 family (PP1), and we identified protein phosphatase 1 alpha isoform (PP1 alpha) as the specific PP1 isoform to mediate this phenotype. Using a bioinformatics approach, we build a functional interaction network based on phosphoproteomics data on plasma membrane ceramide. This led to the identification of several ceramide-PP1 alpha downstream substrates. Studies on phospho mutants of ezrin (T567) and Scrib (S1378/S1508) demonstrated that their dephosphorylation is sufficient to enhance cell migration. In summary, we identified a mechanism where reduced doses of doxorubicin result in the dysregulation of cytoskeletal proteins and enhanced cell migration. This mechanism could explain the reported effects of doxorubicin worsening cancer metastasis in animal models.

Background Due to the unique pathophysiology with progressive mircocirculatory obstruction and simultaneously increased vascular permeability, overhydration can be rapidly harmful in patients with falciparum malaria. The outcome in all 558 cases hospitalised during 2001–2015 in the Charité University Hospital, Berlin, was favourable, independent of the antimalarial used. Here, the fluid management strategy in the most severely affected subgroup is examined. Methods All fluids in 32 patients requiring treatment on intensive care units (ICUs) for >48 h were retrospectively quantified. All malaria-specific complications were followed up over the whole ICU stay. Results Strong linear relationships between fluid intake and positive balances reflecting dehydration and increased vascular permeability were evident over the whole stay. With 2.2 (range: 0.7–6.9), 1.8 (0.6–6.1) and 1.3 (0.3–5.0) mL/kg/h on day 1, day 2 and over the remaining ICU stay, respectively, median fluid volumes remained below the actual WHO recommendations. No evidence for deterioration of any malaria-specific complication under such restrictive fluid management was found. The key prognostic parameter metabolic acidosis improved significantly over 48 h (p=0.02). All patients survived to discharge. Conclusions These results suggest that in the face of markedly increased vascular permeability, a restrictive fluid management strategy is clinically safe in adults with severe imported falciparum malaria.

Air pollution has been associated with adverse health effects across the life-course. Although underlying mechanisms are unclear, several studies suggested pollutant-induced changes in transcriptomic profiles. In this meta-analysis of transcriptome-wide association studies of 656 children and adolescents from three European cohorts participating in the MeDALL Consortium, we found two differentially expressed transcript clusters (FDR p < 0.05) associated with exposure to particulate matter < 2.5 mu m in diameter (PM2.5) at birth, one of them mapping to the MIR1296 gene. Further, by integrating gene expression with DNA methylation using Functional Epigenetic Modules algorithms, we identified 9 and 6 modules in relation to PM2.5 exposure at birth and at current address, respectively (including NR1I2, MAPK6, TAF8 and SCARA3). In conclusion, PM2.5 exposure at birth was linked to differential gene expression in children and adolescents. Importantly, we identified several significant interactome hotspots of gene modules of relevance for complex diseases in relation to PM2.5 exposure. The research leading to these results has received funding from the European Community's Seventh Framework Program under grant agreement numbers: 211,250 (ESCAPE), and 261,357 (MeDALL), and the European Research Council (grant agreement number 757919, TRIBAL). NL was recipient of ANR-15-IDEX-02 grant. BAMSE: BAMSE was supported by The Swedish Research Council, The Swedish Heart-Lung Foundation, Region Stockholm, the Strategic Research Programme (SFO) in Epidemiology at Karolinska Institutet, The Swedish Research Council Formas and the Swedish Environment Protection Agency, the Swedish Asthma and Allergy Research Foundation, the Cancer and Allergy Foundation. O. Gruzieva is supported by the Swedish Research Council for Health, Working life and Welfare (FORTE 2017-01146). GINIplus: The GINIplus study was mainly supported for the first 3 years of the Federal Ministry for Education, Science, Research and Technology (interventional arm) and Helmholtz Zentrum Munich (former GSF) (observational arm). The 4 year, 6 year, 10 year and 15 year follow-up examinations of the GINIplus study were covered from the respective budgets of the 5 study centres (Helmholtz Zentrum Munich (former GSF), Research Institute at Marien-Hospital Wesel, LMU Munich, TU Munich and from 6 years onwards also from IUF -Leibniz Research-Institute for Environmental Medicine at the University of Dusseldorf) and a grant from the Federal Ministry for Environment (IUF Dusseldorf, FKZ 20462296). Further, the 15-year follow-up examination of the GINIplus study was supported by the Commission of the European Communities, the 7th Framework Program: MeDALL project, and as well by the companies Mead Johnson and Nestle. INMA: INMA project was mainly supported by the Commission of the European Community, the 7th Framework Program: MeDALL project and by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; PI04/1436; PI06/0867; PI08/1151; and PI18/01142 incl. FEDER funds), and Generalitat de Catalunya-CIRIT 1999SGR 00241, Department of Health of the Basque Government (2005111093), Provincial Government of Gipuzkoa (DFG06/002), and annual agreements with the municipalities of the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain)

Orientador: José Régis Azevedo Varão Filho Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Matemática, Estatística e Computação Científica Resumo: O objetivo desta dissertação é estudar detalhadamente o artigo Invariant measures for frequently hypercyclic operators de S. Grivaux e É. Matheron. Estudaremos condições para que operadores frequentemente hipercíclicos admitam algumas classes de medidas invariantes com suporte total, como por exemplo medidas ergódicas e contínuas. Em particular, vamos ver que operadores frequentemente hipercíclicos em espaços de Banach separáveis admitem medidas invariantes com suporte total contínuas. Também estudaremos um exemplo de operador frequentemente hipercíclico que não admite medida ergódica com suporte total e duas famílias de probabilidades que nos darão exemplos de operadores frequentemente hipercíclicos que admitem medida ergódica com suporte total. Abstract: The goal of this dissertation is to study the article Invariant measures for frequently hypercyclic operators by S. Grivaux and É. Matheron in detail. We shall study conditions for frequently hypercyclic operators to admit some classes of invariant measures with full support, such as ergodic and continuous measures. Particularly, we will see that frequently hypercyclic operators in separable Banach spaces admit invariant measures with full support. We will also study an example of a frequently hypercyclic operator which does not admit an ergodic measure with full support and two families of probabilities that will give us examples of frequently hypercyclic operators that admit ergodic measure with full support. Mestrado Matemática Mestre em Matemática CNPQ 132320/2019-3

In this paper a spacecraft rendezvous policy is developed that yields safe rendezvous trajectories under various thruster failure scenarios. The policy makes use of polytopic robust backwards reachable sets to characterize the state-space that under a given thruster failure scenario would lead to collision between a deputy and a chief spacecraft no matter the remaining available thrust. That is, this region of state-space is such that no feasible evasive abort maneuver exists for the given failure scenario. Abort-safety constraints are formulated as local hyperplanes separating the deputy spacecraft and the unsafe state-space. These constraints are incorporated in a model predictive control-based online trajectory generation scheme in order to guide the deputy to rendezvous with its chief through an inherently safe approach. Simulations demonstrate the effectiveness of the safety constraints in altering a nominally unsafe rendezvous to one that is abort-safe.

The presence of extreme hydrometeorological threats has co-occurred with the COVID-19 pandemic, increasing the potential risk of a disaster scenario occurring. The hurricane &ldquo, Cristobal&rdquo, which impacted Mexico&rsquo, s tropical regions, presented a high risk of contagion and death caused by the combined effects of violent winds, floods, and evacuations. This work aims to determine whether the presence of concurrent events during the pandemic caused an increase in confirmed positive COVID-19 cases in the Yucatan Peninsula&rsquo, s western sector. To achieve this, a numerical analysis and identification of the tropical storm&rsquo, s extreme characteristics were conducted. Next, a combined analysis of the territorial system subject to flooding and the rainfall level reported during the emergency period was conducted at the municipal level. The third phase consisted of analyzing the confirmed positive cases of COVID-19 at the municipal level on four strategic dates (before, during, observation, and end of the emergency period). Finally, a content analysis of the emergency bulletins, action guides, and disaster declarations was carried out to identify the measures and adaptations implemented during the pandemic. It is recognized that emergency management measures were implemented for municipalities with more than 30 confirmed positive cases of COVID-19 and where the shelter capacity was reduced. Protocols for caring for people were followed, these being one of the leading adaptive methods. From the analyzed data, it can be pointed out that there is no direct evidence for an increase in positive COVID-19 cases in 10 of the municipalities. However, in the case of the municipality of Escarcega, there was a sudden increase in cases from June 8, which continues to grow. Therefore, it is necessary to deepen the study of multiple events to recognize the actions that can prevent catastrophes in these times of crisis.

The emergence of germ layers in embryos during gastrulation is a key developmental milestone. How morphogenetic signals engage the regulatory networks responsible for early embryonic tissue patterning is incompletely understood. To understand this, we developed a gene regulatory network (GRN) model of human pluripotent stem cell (hPSC) lineage commitment and embedded it into ‘cellular’ agents that respond to a dynamic signalling microenvironment. We found that cellular pattern order, composition, and dynamics were predictably manipulable based on the GRN wiring. We showed that feedback between OCT4, and BMP and WNT pathways created a dynamic OCT4 front that mediates the spatiotemporal evolution of developmental patterns. Translocation of this radial front can be predictively disrupted in vitro to control germ-layer pattern composition. This work links the emergence of multicellular patterns to regulatory network activity in individual hPSCs. We anticipate our approach will help to understand how GRN structure regulates organogenesis in different contexts.

Air pollution has been associated with adverse health effects across the life-course. Although underlying mechanisms are unclear, several studies suggested pollutant-induced changes in transcriptomic profiles. In this meta-analysis of transcriptome-wide association studies of 656 children and adolescents from three European cohorts participating in the MeDALL Consortium, we found two differentially expressed transcript clusters (FDR p 0.05) associated with exposure to particulate matter 2.5 µm in diameter (PM

© The Author(s) 2021., Small Open Reading Frames (smORFs) coding for peptides of less than 100 amino-acids are an enigmatic and pervasive gene class, found in the tens of thousands in metazoan genomes. Here we reveal a short 80 amino-acid peptide (Pegasus) which enhances Wingless/Wnt1 protein short-range diffusion and signalling. During Drosophila wing development, Wingless has sequential functions, including late induction of proneural gene expression and wing margin development. Pegasus mutants produce wing margin defects and proneural expression loss similar to those of Wingless. Pegasus is secreted, and co-localizes and co-immunoprecipitates with Wingless, suggesting their physical interaction. Finally, measurements of fixed and in-vivo Wingless gradients support that Pegasus increases Wingless diffusion in order to enhance its signalling. Our results unveil a new element in Wingless signalling and clarify the patterning role of Wingless diffusion, while corroborating the link between small open reading frame peptides, and regulation of known proteins with membrane-related functions., This work was funded by grants from the British BBSRC (ref. BB/N001753/1) and the Spanish MINECO (refs. BFU2016-077793-P, MDM-2016-0687) and MCI (PID2019-106227GB-I00).

Morphogen gradients are fundamental to establish morphological patterns in developing tissues

Multi-Drug Resistant (MDR) microorganisms are defined as microorganisms, predominantly bacteria, resistant to one or more class of antimicrobial agents...

Background Crohn’s disease (CD) is a multifactorial disease characterized by chronic intestinal inflammation. The increased visceral adiposity near the affected intestinal area, of which mesenteric adipose tissue (MAT) is the main component, is a feature of CD. Both protective and pathological roles have been attributed to this disease-associated tissue in CD. To understand the contribution of MAT to CD pathophysiology, a molecular and cellular signature of disease-associated MAT in CD patients was provided. Methods We performed an observational study with whole transcriptional analysis by RNA sequencing (RNA-seq) of MAT and ileal mucosa from CD patients with active disease and controls. qPCR and immunohistology were performed for validation analysis. Results RNA-seq identified 17 significantly regulated genes (|FC| > 1.5; FDR 1.5, nominal p ≤ 0.05) yielded a larger list of 651 genes in CD-MAT compared to controls. CD ileum showed the significant regulation compared to control ileum of 849 genes (|FC| > 1.5; FDR 1.5, nominal p ≤ 0.05). Ingenuity Pathway Analysis revealed the significant regulation of pathways related to T- and B cell functionality in the MAT of CD patients. Despite the differences between the MAT and ileal signatures of CD patients, we identified a subset of 204 genes significantly modulated in both tissues compared to controls. This common signature included genes related to the plasma cell signature. Genes such as S100A8, S100A9 (calprotectin) and IL1B, which are associated with acute inflammatory response, were exclusively regulated in the ileal mucosa of CD disease. In contrast, some genes encoding for lymphocyte receptors such as MS4A1, CD3D and CD79A were exclusively regulated in CD-MAT, exhibiting a different pattern of immune cell activation compared to the ileal mucosa in CD patients. qPCR and immunohistology confirmed the presence of large infiltrates of CD3+ CD20+ lymphocytes and CD138+ plasma cells in CD-MAT. Conclusion Our data strongly supports the role of CD-associated MAT as a site for T-, B- and plasma cell activation, and suggests that it could also act as a reservoir of memory immune responses.

Small-scale fisheries are vital for food security, nutrition, and livelihoods in coastal areas throughout the world's oceans.

Objective To evaluate and compare the analgesic efficacy and adverse effects of dexketoprofen and methadone using a noninferiority trial, during the first 24 postoperative hours in dogs undergoing orthopaedic surgery. Study design Randomized, blinded clinical study. Animals A total of 38 healthy dogs undergoing orthopaedic surgery. Methods Dogs were premedicated with dexmedetomidine [1 μg kg–1 intravenously (IV)] followed by dexketoprofen (1 mg kg–1 IV; group DK) or methadone (0.2 mg kg–1 IV; group M). Anaesthesia was induced with propofol and maintained with isoflurane in 60% oxygen. Postoperatively, dexketoprofen was administered every 8 hours (group DK) and methadone every 4 hours (group M). Analgesia was assessed at baseline and at 1, 2, 4, 6, 18 and 24 hours after extubation using a dynamic and interactive visual analogue scale (DIVAS), the short form of the Glasgow Composite Measure Pain Scale (CMPS-SF), mechanical wound thresholds (MWTs) and plasma cortisol levels. If CMPS-SF score was ≥5, rescue analgesia was administered. Data were analysed using a general linear mixed model, Mann–Whitney U test and chi-squared test as appropriate; a p value Results The CMPS-SF and DIVAS scores were significantly higher in group M compared with group DK and remained higher for a longer period in group M, although the differences were not clinically significant. No significant differences were found in MWT assessment between groups. Plasma cortisol level significantly increased 2 hours after extubation, without significant differences between treatments. Rescue analgesia was administered to three animals (one in group DK; two in group M). Conclusion and clinical relevance We conclude that 1 mg kg–1 IV dexketoprofen administered every 8 hours during the first 24 hours postoperatively is noninferior to methadone in controlling pain after orthopaedic surgery in dog, although frequent pain assessments are recommended to adjust the analgesia plan.

During the past decades, many authors have studied extreme ozone ( O 3 ) events on successive days in several cities around the world, where extreme pollution concentrations are considered as values exceeding air quality standards. These multiday episodes are caused by different variables: weather conditions, pollution precursors life times and air pollution transport. However, a complete characterization of the temporal behavior of multiday extreme O 3 episodes is still lacking. In the present paper, we used the Haar wavelet transform to study the period (T in days) of multiday extreme O 3 episodes in Mexico city during 2015–2016, when 10 ozone contingencies occurred and changes in driving restrictions were implemented. In addition, we studied the temporal correlations between extreme O 3 and extreme: nitrogen dioxide ( NO 2 ), carbon monoxide (CO) and ultraviolet B radiation (UVB) for a broad range of time scales by means of the Haar Wavelet cross-correlation method. The results show that multiday O 3 episodes mainly exhibit periods of T > 4 days, while NO 2 and CO show multiday episodes comprising principally periods of T > 2 days. The cross correlation analysis reveals that CO and NO 2 are temporal anti-correlated with O 3 for daily variations T 1 . However, NO 2 and CO are strongly and moderately correlated with O 3 for T > 4 , respectively, indicating that NO 2 , CO and O 3 are correlated in a multi-temporal clustered form.

Este artículo se encuentra disponible en la página web de la revista en la siguiente URL: https://www.tandfonline.com/doi/full/10.1080/09712119.2017.1337017 Tendon injuries are the most frequent musculoskeletal problems, constituting 30–50% of all sport-related lesions. Efficient handling of early stage tendon injury and healing can accelerate tendon repair as well as improve the quality of newly formed tendons. Plasma rich in growth factors (PRGF) is an autologous biological therapy that has been proposed to treat tendon injuries. To elucidate the effect of this treatment on the early stage of tendon healing, 14 sheep were used to perform the present study. The right Achilles tendon was surgically severed and repaired with sutures. Seven animals were treated with PRGF and the other seven with saline solution after surgical tendon reconstruction. Tendons were ultrasound-guide infiltrated 1 week after the induced injury. Two weeks later, the sheep were euthanized and histochemical and immunohistochemical analyses were performed. The tendons with PRGF showed reduced infiltration of inflammatory cells compared to those treated with saline solution. Analysis of the blood vessels, morphometric data of fibroblast nuclei, and collagen fibres in the extracellular matrix did not show statistical differences between groups. These findings suggest the important role that PRGF therapy plays in the modulation of inflammatory response in Achilles tendon injuries, leading to acceleration of the tendon healing process, shortening the convalescence period.

Background Patients with severe SARS-CoV-2 infection are at high risk of complications due to the intensive care unit stay. Hospital-acquired infections (HAI) are one of the most common complication and cause of death in this group of patients, it is important to know the epidemiology and microbiology of this hospital-acquired infections in order to begin to the patients a proper empirical treatment. We describe the epidemiologic and microbiologic characteristics of HAI in patients with COVID-19 hospitalized at intensive care unit (ICU) in a tertiary level private hospital in Mexico City. Methods From April to December 2020, data from all HAIs in patients with severe pneumonia due to SARS-CoV-2 infection with mechanical ventilation at ICU were obtained. The type of infection, microorganisms and antimicrobial susceptibility patterns were determined. Results A total of 61 episodes of HAIs were obtained, the most common was ventilator associated pneumonia (VAP) in 52.4% (n=32) followed by urinary tract infection (UTI) 34.4%(n=21) and bloodstream infection (BSI) 9.84% (n=6). Only two episodes corresponded to C. difficile associated diarrhea. We identified 82 different microorganisms, the most frequent cause of VAP was P. aeruginosa 22% (10/45) followed by K. pneumoniae 20% (9/45); for UTI, E. coli 28.5% (6/21), and S. marcescens 19% (4/21); for BSI the most frequent microorganism was S. aureus 28.5 (2/7). Regarding the antimicrobial susceptibility patters the most common were Extended Spectrum Beta-Lactamase (ESBL) Gram-negative rods followed by Methicillin-resistant Staphylococcus aureus. Conclusion In patients with severe COVID-19 hospitalized in the ICU the most frequent HAIs were VAP and UTI caused by P. aeruginosa and E. coli respectively. ESBL enterobacteriaceae was the most common resistant pattern identifed in the bacterial isolations in our series. Disclosures All Authors: No reported disclosures